The research will employ synthetic polymers of amino acids (random and sequential) to study aspects of immunogenicity and genetic control of the immune response (Ir), in mice and guinea pigs. The polymers have been T cell dependent and "histocompatibility-linked". The strain distribution patterns in inbred mice and guinea pigs will be studied. Immune responses will measure both antibody in the serum, (antigen binding assays) and specific plaque-forming cells (B cells), and the in vitro stimulation of peritoneal exudate T lymphocytes (PETLES). Comparisons will be made of T cell and B cell specificities by reactions with related polymers. Using recombinant inbred strains of mice, the Ir genes controlling responses will be mapped to areas within the I subregion in the mouse H2 comples. Cellular aspects, notably the involvement of thymus-derived antigen-reactive cells (T cells) in unresponsiveness, i.e., suppressor T cells, T cell antigen binding specificity, both at the cellular and subcellular levels, will be compared with the known humoral responses to the polymers. 125I-labelled polymers will be used in binding experiments with purified T cells obtained by nylon wool column techniques. The characterization of the nature of the receptor(s) will include experiments to determine possible association of "la antigens" with the antigen specific receptor. With the nonimmunogenic polymers, we will determine whether immune suppressor (Iso) genes control nonresponsiveness, and whether "gene complementation" might lead to responsiveness. Affinity chromatography techniques will be employed to isolate and characterize antigen-specific suppressor and helper factors as well as "T cell receptors". Reinvestigations of responses of mice of H-2s haplotype against GAT10, and studies on the effects of preparation and treatments of the polymers on responses will be undertaken. The B cell mitogenic activity (mice) of sequential polymers will be investigated to determine whether these polymers are "specific" or "Polyclonal" mitogens. The antibody produced in some of the "genetically controlled" systems will be isolated and studied for possible homogeneity properties. The preparation of anti-idiotypic antibodies will be undertaken.